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Electronic Case Report Form Initiative

COVID-19-related data elements in the eCRF for current and future oncology clinical trials

The FDA Oncology Center of Excellence (OCE) and the LUNGevity Foundation brought together stakeholders from industry and the FDA to discuss the future of cancer clinical trials in a post-COVID-19 era, with the goal of ensuring continued progress in cancer drug therapy development. This working group focused on COVID-19-related elements for the Electronic Case Report Form (eCRF) for current and future clinical trials with the goal of a general agreement with respect to what and how COVID-19-related data elements will be included in future clinical study report (CSR) submissions to the FDA.

The following recommendations are indicative of shared approaches and best practices for sponsors of oncology product clinical trials with regard to preparing and submitting eCRFs and CSRs for clinical trials conducted during the COVID-19 pandemic.

General Considerations

  • The following recommendations should be viewed as supporting, to the extent possible, the inclusion of patients with a history of COVID-19 in oncology clinical trials and subsequent data analyses.
  • FDA cannot mandate what data are collected on eCRFs. It is recommended that companies collect as much COVID-19-related data as feasible without undue burden for trials sites and investigators.
    • For example, it is recommended that COVID-19 vaccination status be collected; beyond that, the level of granularity in terms of vaccine type, date(s) of administration, lot numbers, etc., is at the sponsor’s discretion.
  • FDA is expecting a high rate of protocol deviations for trials conducted during the COVID-19 pandemic, as well as a higher-than-normal rate of adverse events. Sponsors will not be penalized for reporting deviations and adverse events.
  • In the absence of formal guidance, sponsors are encouraged to present their COVID-19 data reporting plans to the FDA during pre-BLA/NDA meetings for study-level approval.

Recommendations Related to Safety Analyses of the Impact of COVID-19

  • Use COVID-19-specific Standardized MedDRA Query (SMQ; version 23.1) preferred terms (PT) for COVID-19-associated adverse event (AE) monitoring and reporting.
    • Sponsors do not have to use all updated PTs but should present their rationale for (not) doing so.
    • Sponsors should decide for themselves whether and which COVID-19 symptoms to collect as AEs.
    • Sponsors should decide for themselves, with scientific justification, for how long to monitor associated events in patients with known COVID diagnoses (e.g., 21 days, 30 days, etc.). Similarly, for how long to follow patients whose discontinuation of a trial was due to COVID-associated AEs.
  • Collection of “long-term” COVID-associated events should be done in a separate table.
    • Flagging any unexpected event or toxicity in patients with history of COVID-19 infection, whether or not it meets the definition of adverse event for the study, will help determine the nature and extent of COVID-19-associated events in future analyses.
  • When known, note drugs used for treatment of COVID-19 in concomitant medication tables and list potential interactions (ex: hydroxychloroquine may affect efficacy of antibody-drug conjugates that require lysosomal-based linker cleavage)
  • Flag deaths and perform sensitivity analyses for post-COVID patients who die while on-study.

Recommendations Related to Reporting of Protocol Modifications Due to COVID-19

  • Sponsors should determine what constitutes “major” and “minor” protocol deviations for each study as well as how those will be handled (e.g., all deviations documented in eCRF and reported in CSR, or all deviations documented but only major deviations reported in CSR, or other).
  • Sponsors should decide on a study-by-study bases which modifications have had the greatest impact on study integrity and present those to the FDA in terms of safety and efficacy.
  • Sponsors should identify whether assessments are conducted at the clinical site or remotely to facilitate dataset flags that can allow FDA to assess potential effects of remote trial conduct (see “Advancing Oncology Decentralized Trials”).

Additional Information

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